Longevity Meme Newsletter, June 08 2009

June 08 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.



- h+ Magazine Summer Issue
- An Update on Decellularization / Recellularization
- Odds of Human Single Gene Longevity Mutations
- Discussion
- Latest Healthy Life Extension Headlines


The new h+ Magazine is reminiscent of the old, more adventurous Wired, but with much more of a slant towards life sciences and longevity engineering.


"As the Boomers begin to go gray and fragile, those with way high expectations confront an uncomfortable fact - nobody has done much about aging, throughout their lifetimes ... and they get angry. How could this be?! Technology has carried us along on its broad back, giving us computers, conveniences, Internet and media wonders. But aches and pains foretell much bad news ahead. We can do better, but to do it we'll have to reinvent biology."

This is as good a distillation as you'll see of the spirit that drives the more active members of the pro-longevity mainstream of biogerontology. They work to build a better human metabolism, one small piece at a time: a biochemistry of life that will last longer. As usual, I should remind you that this vision looks like the slow and hard road from where I stand. There is an alternative: don't rework this incredibly complex system, but rather learn to reverse the fundamental forms of change and damage that cause it to fail. Build a better metabolism and it'll still fail in time. Learn to repair and restore the metabolism we have, and it'll last as long as you care to keep working on it.


More research groups are now working on stripping donor organs of cells, leaving only the extracellular matrix behind, and then repopulating it with the recipient's own cells:


"The rat hearts beat just as if there were inside a live animal, but even more remarkable is how each one has been made: by coating the stripped-down 'scaffolding' of one rat's heart with tissue grown from another rat's stem cells. ... This could lead to a virtually limitless supply of organs for transplantation that are every bit as intricate as those that grow naturally ... 'We're already working with heart, kidney, liver, lung, pancreas, gallbladder and muscle,' Taylor says. Rival groups are using similar procedures to create new livers and muscle too."

Researchers also note that recellularized organs are a solution to one of the other bugbears of tissue engineering: how to produce the intricate array of blood vessels needed to sustain tissue, and then successfully patch it in to a transplant recipient's existing blood transport system. Because the extracellular matrix structure retains the blood vessels, they can hook it up to the recipient's natural blood supply. There are a least a few people from early trials and demonstrations presently walking around with not-so-small chunks of recellularized tissue in their bodies, blood vessels and all: heart valves and a trachea for example.



What are the odds of significant life extension in humans through a single mutation, such as those discovered in mice and lower animals?


"Based on what I've seen over the past decade, I would not be surprised to see mouse life span doubled ten years from now through some ingenious combination of simple gene engineering and altered cellular processes - i.e. through slowing aging rather than repairing damage. Researchers are already half way there. Equally, I would not be surprised to see single human genes discovered that when manipulated or silenced can produce an expected change in life expectancy on a par with the expected changes for exercise and calorie restriction. This is to say something between a few years to an additional decade of healthy life, and an unknown effect on maximum life span."

I would be very surprised if anything greater than that jumps out of a single gene mutation in humans, however.


The highlights and headlines from the past week follow below.

Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!




Why Aging? (June 05 2009)
Why do organisms age? At the cellular and bacterial level, one can argue that aging is an inevitable evolved optimization that aims to carefully distribute biochemical damage to best ensure the continuing survival of a line of descent. But how and why did evolution favor aging in higher animals? Here's one line of thought: researchers "postulate that senescence could have evolved in order to prevent the spread of disease epidemics in populations ... Population density is a robust measure of fitness. But, paradoxically, the risk of lethal epidemics which can wipe out an entire population rises steeply with population density. We explore an evolutionary dynamic that pins population density at a threshold level, above which the transmissibility of disease rises to unacceptable levels. Population density can be held in check by general increases in mortality, by decreased fertility, or by senescence. We model each of these, and simulate selection among them. In our results, senescence is robustly selected over the other two mechanisms, and we argue that this faithfully mirrors the action of natural selection. This picture constitutes a mechanism by which senescence may be selected as a population-level adaptation in its own right."

Call For Submissions to Hourglass X (June 05 2009)
If you're in the habit of posting on the topic of aging science, then give some thought to submitting a recent post to the next Hourglass blog carnival: "The tenth installation of Hourglass, a monthly blog carnival devoted to the best blogging about biology of aging, will appear here at Ouroboros on Tuesday, June 9th ... Topics of posts should have something to do with the biology of aging, broadly speaking - including fundamental research in biogerontology, age-related disease, ideas about life extension technologies, your personal experience with calorie restriction, maybe even something about the sociological implications of increased longevity. Opinions expressed are not necessarily those of the management, so feel free to subvert the dominant paradigm. If in doubt, submit anyway. ... By the way, if you'd like to volunteer to host, please [contact Chris Patil at Ouroboros] - basically the rest of 2009 is wide open. If you've already hosted before, don’t let that hold you back; while the carnival is young, some repeat hosting is going to be par for the course."

Enhancing Muscle Regeneration (June 04 2009)
In many situations we won't always need stem cell transplants to build a regenerative therapy. In theory, with sufficient understanding, we could instruct existing stem cells in the body to do the job instead: researchers "have discovered a powerful new way to stimulate muscle regeneration, paving the way for new treatments for debilitating conditions such as muscular dystrophy. The research [shows] for the first time that a protein called Wnt7a increases the number of stem cells in muscle tissue, leading to accelerated growth and repair of skeletal muscle. ... This discovery shows us that by targeting stem cells to boost their numbers, we can improve the body's ability to repair muscle tissue ... the Wnt7a protein, when introduced into mouse muscle tissue, significantly increased the population of these satellite stem cells and fueled the regeneration process, creating bigger and stronger muscles. Muscle tissue mass was increased by nearly 20 per cent in the study. ... Our findings point the way to the development of new therapeutic treatment for muscular diseases such as muscular dystrophy, sarcopenia and muscle wasting conditions resulting from extended hospital stays and surgeries."

An Example of Corneal Regeneration (June 04 2009)
From the Australian: "Three Australians have had their sight restored thanks to their own stem cells and ordinary contact lenses. Although the novel technique was used to reverse blinding corneal disease, it promises to be a quick, painless and cheap treatment for other visual disorders. It may even be useful for repairing damaged skin ... We're quietly excited. We don't know yet if (the correction) will remain stable, but if it does it's a wonderful technique ... two of the three patients were legally blind in the treated eye; they can now read big letters on the eye chart. The third could read the top few rows of the chart but is now able to pass the vision test for a driving license. ... the idea to team stem cells with contact lenses came from an observation [that] stem cells from the cornea, or front of the eye, stick to contact lenses. To obtain the stem cells, Dr Watson took less than a millimeter of tissue from the side of each patients' cornea [and] cultured stem cells from the tissue in extended wear contact lenses. Dr Watson then cleaned the surface of the patients' corneas and inserted the lenses. Within 10 to 14 days the stem cells began to attach to the cornea, replenishing damaged."

Increasing the Feasibility of Xenotransplantation (June 03 2009)
Xenotransplantion looks like a viable mid-term technology - after biotechnology can make animal transplants effective and very safe, but before biotechnology has advanced to the point of creating human organs from scratch. From the Times Online: "Scientists in China have successfully reprogrammed pig skin and bone marrow cells into an embryo-like state with the potential to form every type of body tissue. The achievement promises to provide a tool for breeding pigs that are genetically engineered to carry human immune system proteins so that their organs are less likely to be rejected for transplant. ... Pig pluripotent stem cells would be useful in a number of ways, such as precisely engineering transgenic animals for organ transplantation therapies. The pig species is significantly similar to humans in its form and function, and the organ dimensions are similar to human organs. We could use embryonic stem cells or induced stem cells to modify the immune-related genes in the pig to make the pig organ compatible to the human immune system. Then we could use these pigs as organ donors to provide organs for patients that won’t trigger an adverse reaction from the patient’s own immune system."

Regenerating Lost Hair (June 03 2009)
We humans are driven by vanity. I'd give fair odds that tissue engineering of new hair will be widely available before tissue engineering of the simpler internal organs. Here's an example progress in this field: "Professor Lin Sung-jan took 10 hair follicles from rodents and cultivated 8 to 10 million dermal papilla cells in vitro in 20 days. Using aggregates of between 3 and 5 million dermal papilla cells, he mixed these with rodent skin cells and transplanted them onto bare rodent skin, which sprouted hair. ... Discovering that dermal papilla cells function to send signals and implement instructions, Lin developed biomaterial that can assemble and produce such cells. He also developed a bio-reaction device for use in mass-producing micro-tissues to induce hair follicle regeneration. Lin has also taken human hair follicles and conducted similar experiments, successfully growing hair on the skin of rodents. In future, he hopes to be able to control the size and color of hair grown."

Elastin and Aging Arteries (June 02 2009)
Damage to the elastin in the walls of our arteries is one of the ways in which we age: "Aging affects elastin, a key component of the arterial wall integrity and functionality. Elastin degradation in cerebral vessels is associated with cerebrovascular disease. ... The structural morphology of elastin changed [with age] from a fiber network oriented primarily in the circumferential direction to a more heterogeneously oriented fiber mesh ... Biomechanically, cerebral arteries stiffen with age ... Enzymatic degradation of elastin led [to] stiffening in the young group but did not affect the structural and material properties in the older group, suggesting that elastin, though present in equal quantities in the old group, becomes dysfunctional with aging. ... Elastin loses its functionality in cerebral arteries with aging, leading to stiffer less compliant arteries. The area fraction of elastin remained, however, fairly constant. The loss of functionality may thus be attributed to fragmentation and structural reorganization of elastin occurring with age." This has the look of the sort of damage done by accumulating senescent cells, which emit biochemicals that lead to errant remodeling of the surrounding extracellular matrix.

Indy Looks Like a Calorie Restriction Mechanism (June 02 2009)
The INDY longevity gene in flies looks like it works via reducing mitochondrial free radicals, amongst other items. Here's more evidence to show that calorie restriction (CR) triggers INDY, and there is at least some of the benefit gained: "The Drosophila gene Indy (for I'm not dead yet), involved in the transport and storage of Krebs cycle intermediates in tissues important in fly metabolism, was proposed to regulate life span via an effect on metabolism that could overlap with CR. In this study, we report that CR down regulates Indy mRNA expression, and that CR and the level of Indy expression interact to affect longevity. Optimal life span extension is seen when Indy expression is decreased between 25 and 75% of normal. Indy long-lived flies show several phenotypes that are shared by long-lived CR flies, including decreased insulin-like signaling, lipid storage, weight gain, and resistance to starvation as well as an increase in spontaneous physical activity. We conclude that Indy and CR interact to affect longevity and that a decrease in Indy may induce a CR-like status that confers life span extension."

Prospects For Combined Gene and Stem Cell Therapy (June 01 2009)
Here is news of a technology demonstration that hints the future of medicine, "proving in principle that a human genetic disease can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology ... The hope in the field has always been that we'll be able to correct a disease genetically and then make iPS cells that differentiate into the type of tissue where the disease is manifested and bring it to clinic ... After taking hair or skin cells from patients with Fanconi anemia, the investigators corrected the defective gene in the patients' cells using gene therapy techniques ... They then successfully reprogrammed the repaired cells into induced pluripotent stem (iPS) cells ... Since bone marrow failure as a result of the progressive decline in the numbers of functional hematopoietic stem cells is the most prominent feature of Fanconi anemia, the researchers then tested whether patient-specific iPS cells could be used as a source for transplantable hematopoietic stem cells. They found that [the] cells readily differentiated into hematopoietic progenitor cells primed to differentiate into healthy blood cells. ... We haven't cured a human being, but we have cured a cell. In theory we could transplant it into a human and cure the disease."

An Exception to the General Rule (June 01 2009)
Ouroboros looks at a rare example of a treatment that extends life span but shortens healthspan in flies: "One of the central precepts of biogerontology is that meaningful lifespan extension will be concomitant with extension of the 'healthspan', i.e., the vigorous part of life - life that is, for lack of a better phrase, worth living. This relationship is borne out both in nature (where longer-lived organisms also have longer healthspans) and in the laboratory, where genetic and pharmaceutical manipulations increase longevity also increase the duration of healthy life ... Because of the importance of this assumption, we need to be on the lookout for counterexamples, such as the one provided by a recent study ... The authors show that lamotrigine, an anticonvulsant medication already shown to extend lifespan in the worm C. elegans, also has longevity benefits in the fly - but at an apparent cost to healthspan. ... the existence of exceptions to the general case underscores the importance of vetting each candidate longevity enhancement therapy for its effects on healthspan, before rushing into further development."



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